SFTPC

N-terminalni propeptidni surfaktantni protein C
N-terminalni propeptidni surfaktantni protein C
	Svinjski SP-C koji korespondira sa ljudskim zrelim oblikom
Identifikatori
Simbol	SP_C-Propep

SFTPC
Dostupne strukture
PDB	Pretraga ortologa: PDBe RCSB
Spisak PDB ID kodova
	2YAD
Identifikatori
Aliasi	SFTPC
Vanjski ID-jevi	OMIM: 178620 MGI: 109517 HomoloGene: 2271 GeneCards: SFTPC
Lokacija gena (čovjek)
Hrom.	Hromosom 8 (čovjek)
Kraj	22,164,479 bp
Lokacija gena (miš)
Hrom.	Hromosom 14 (miš)
Kraj	70,761,521 bp
Obrazac RNK ekspresije
	; ; ; ;
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• GO:0001948, GO:0016582 vezivanje za proteine; • vezivanje identičnih proteina;
Ćelijska komponenta	• extracellular region; • clathrin-coated endocytic vesicle; • lamellar granule; • endoplasmic reticulum membrane; • multivesicular body lumen; • Vanćelijsko;
Biološki proces	• respiratory gaseous exchange by respiratory system;
	Izvori:Amigo / QuickGO
Ortolozi
	6440
	20389
	ENSG00000168484
	ENSMUSG00000022097
	P11686
	P21841; Q6P8P8
NM_001172357; NM_001172410; NM_003018; NM_001317778; NM_001317779;
	NM_001317780
	NM_011359
NP_001165828; NP_001165881; NP_001304707; NP_001304708; NP_001304709;
	NP_003009
	NP_035489
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Surfaktantni protein C (SP-C) jedan je od plućnih surfaktantnih proteina. To je membranski protein koji je kod ljudi kodiran genom SFTPC.^[5]^[6]^[7]

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 197 aminokiselina, а molekulska težina 21.053 Da.^[8]

C: Cistein

D: Asparaginska kiselina

E: Glutaminska kiselina

F: Fenilalanin

G: Glicin

H: Histidin

I: Izoleucin

K: Lizin

L: Leucin

M: Metionin

N: Asparagin

P: Prolin

Q: Glutamin

R: Arginin

S: Serin

T: Treonin

V: Valin

W: Triptofan

Y: Tirozin

10	20	30	40	50
MDVGSKEVLM	ESPPDYSAAP	RGRFGIPCCP	VHLKRLLIVV	VVVVLIVVVI
VGALLMGLHM	SQKHTEMVLE	MSIGAPEAQQ	RLALSEHLVT	TATFSIGSTG
LVVYDYQQLL	IAYKPAPGTC	CYIMKIAPES	IPSLEALNRK	VHNFQMECSL
QAKPAVPTSK	LGQAEGRDAG	SAPSGGDPAF	LGMAVNTLCG	EVPLYYI

Struktura

SFTPC 197-aminokiselinski protein sastavljen od dvije polovine: jedinstvenog N-terminalnog propeptidnog domena i C-terminalnog BRICHOS domena. Propeptidni domen dužine oko 100 aa zapravo ne sadrži samo cijepani dio, već i zreli peptid. Može se dalje razgraditi na 23-aminokiselinski spiralni transmembranski propeptid, zreli izlučeni SP-C (24-58) i linker (59-89) koji se povezuje s domenom BRICHOS.^[9]

Propeptid plućnog surfaktanta C ima N-terminalni alfa-heliksni segment čija je predložena funkcija bila stabilizacija proteinske strukture, budući da se zreli peptid može nepovratno transformirati iz svoje nativne alfa-heliksne strukture u agregate beta-listova i formirati amiloidna vlakna. Također je prijavljeno da tačan unutarćelijski promet proSP-C zavisi od propeptida.^[10]

Struktura BRICHOS domena je riješena. Mutacije u ovom domenu također dovode do amiloidnih vlakana sačinjenih od zrelog peptida, što ukazuje na šaperonsku aktivnost.^[9]

Klinički značaj

Mutacije su povezane s disfunkcijom metabolizma surfaktanta tip 2.

Ljudi i životinje rođeni bez SP-C imaju tendenciju razvoja progresivne intersticijske bolesti pluća.

Rekombinantni SP-C koristi se u Venticuteu, vještačkom surfaktantu za pluća.

Opisan je postupak masovne proizvodnje analoga zvanog rSP-C33Le, fuzijom sa spidroinom.^[11]

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000168484 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000022097 - Ensembl, maj 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Keller A, Eistetter HR, Voss T, Schäfer KP (juli 1991). "The pulmonary surfactant protein C (SP-C) precursor is a type II transmembrane protein". The Biochemical Journal. 277 ( Pt 2) (Pt 2): 493–9. doi:10.1042/bj2770493. PMC 1151261. PMID 1859376.
^ Johansson H, Nordling K, Weaver TE, Johansson J (juli 2006). "The Brichos domain-containing C-terminal part of pro-surfactant protein C binds to an unfolded poly-val transmembrane segment". The Journal of Biological Chemistry. 281 (30): 21032–9. doi:10.1074/jbc.M603001200. PMID 16709565.
^ "Entrez Gene: SFTPC surfactant, pulmonary-associated protein C".
^ "UniProt, P11686" (jezik: engleski). Pristupljeno 21. 9. 2021.
^ ^a ^b Willander H, Askarieh G, Landreh M, Westermark P, Nordling K, Keränen H, et al. (februar 2012). "High-resolution structure of a BRICHOS domain and its implications for anti-amyloid chaperone activity on lung surfactant protein C". Proceedings of the National Academy of Sciences of the United States of America. 109 (7): 2325–9. Bibcode:2012PNAS..109.2325W. doi:10.1073/pnas.1114740109. PMC 3289314. PMID 22308375.
^ Li J, Liepinsh E, Almlén A, Thyberg J, Curstedt T, Jörnvall H, Johansson J (mart 2006). "Structure and influence on stability and activity of the N-terminal propeptide part of lung surfactant protein C". The FEBS Journal. 273 (5): 926–35. doi:10.1111/j.1742-4658.2006.05124.x. PMID 16478467. S2CID 1231483.
^ Kronqvist N, Sarr M, Lindqvist A, Nordling K, Otikovs M, Venturi L, et al. (maj 2017). "Efficient protein production inspired by how spiders make silk". Nature Communications. 8 (1): 15504. Bibcode:2017NatCo...815504K. doi:10.1038/ncomms15504. PMC 5457526. PMID 28534479.

Dopunska literatura

Pérez-Gil J (2002). "Lipid-protein interactions of hydrophobic proteins SP-B and SP-C in lung surfactant assembly and dynamics". Pediatric Pathology & Molecular Medicine. 20 (6): 445–69. doi:10.1080/15227950152625783. PMID 11699574.
Solarin KO, Wang WJ, Beers MF (2002). "Synthesis and post-translational processing of surfactant protein C". Pediatric Pathology & Molecular Medicine. 20 (6): 471–500. doi:10.1080/15227950152625792. PMID 11699575.
Johansson J, Curstedt T, Robertson B (2002). "Artificial surfactants based on analogues of SP-B and SP-C". Pediatric Pathology & Molecular Medicine. 20 (6): 501–18. doi:10.1080/15227950152625800. PMID 11699576.
Nogee LM (2004). "Alterations in SP-B and SP-C expression in neonatal lung disease". Annual Review of Physiology. 66: 601–23. doi:10.1146/annurev.physiol.66.032102.134711. PMID 14977415.
Brasch F, Griese M, Tredano M, Johnen G, Ochs M, Rieger C, et al. (juli 2004). "Interstitial lung disease in a baby with a de novo mutation in the SFTPC gene". The European Respiratory Journal. 24 (1): 30–9. doi:10.1183/09031936.04.00000104. PMID 15293602.
Curstedt T, Johansson J, Persson P, Eklund A, Robertson B, Löwenadler B, Jörnvall H (april 1990). "Hydrophobic surfactant-associated polypeptides: SP-C is a lipopeptide with two palmitoylated cysteine residues, whereas SP-B lacks covalently linked fatty acyl groups". Proceedings of the National Academy of Sciences of the United States of America. 87 (8): 2985–9. Bibcode:1990PNAS...87.2985C. doi:10.1073/pnas.87.8.2985. PMC 53818. PMID 2326260.
Simatos GA, Forward KB, Morrow MR, Keough KM (juni 1990). "Interaction between perdeuterated dimyristoylphosphatidylcholine and low molecular weight pulmonary surfactant protein SP-C". Biochemistry. 29 (24): 5807–14. doi:10.1021/bi00476a023. PMID 2383558.
Glasser SW, Korfhagen TR, Perme CM, Pilot-Matias TJ, Kister SE, Whitsett JA (juli 1988). "Two SP-C genes encoding human pulmonary surfactant proteolipid". The Journal of Biological Chemistry. 263 (21): 10326–31. doi:10.1016/S0021-9258(19)81519-3. PMID 2839484.
Glasser SW, Korfhagen TR, Weaver TE, Clark JC, Pilot-Matias T, Meuth J, et al. (januar 1988). "cDNA, deduced polypeptide structure and chromosomal assignment of human pulmonary surfactant proteolipid, SPL(pVal)". The Journal of Biological Chemistry. 263 (1): 9–12. doi:10.1016/S0021-9258(19)57347-1. PMID 3335510.
Johansson J, Jörnvall H, Eklund A, Christensen N, Robertson B, Curstedt T (maj 1988). "Hydrophobic 3.7 kDa surfactant polypeptide: structural characterization of the human and bovine forms". FEBS Letters. 232 (1): 61–4. doi:10.1016/0014-5793(88)80386-7. PMID 3366248. S2CID 29388224.
Warr RG, Hawgood S, Buckley DI, Crisp TM, Schilling J, Benson BJ, et al. (novembar 1987). "Low molecular weight human pulmonary surfactant protein (SP5): isolation, characterization, and cDNA and amino acid sequences". Proceedings of the National Academy of Sciences of the United States of America. 84 (22): 7915–9. Bibcode:1987PNAS...84.7915W. doi:10.1073/pnas.84.22.7915. PMC 299446. PMID 3479771.
Young WA (maj 1966). "Familial fibrocystic pulmonary dysplasia: a new case in a known affected family". Canadian Medical Association Journal. 94 (20): 1059–61. PMC 1935417. PMID 5942662.
Wood S, Yaremko ML, Schertzer M, Kelemen PR, Minna J, Westbrook CA (decembar 1994). "Mapping of the pulmonary surfactant SP5 (SFTP2) locus to 8p21 and characterization of a microsatellite repeat marker that shows frequent loss of heterozygosity in human carcinomas". Genomics. 24 (3): 597–600. doi:10.1006/geno.1994.1673. PMID 7713515.
Hatzis D, Deiter G, deMello DE, Floros J (1994). "Human surfactant protein-C: genetic homogeneity and expression in RDS; comparison with other species". Experimental Lung Research. 20 (1): 57–72. doi:10.3109/01902149409064373. PMID 8181452.
Nogee LM, Dunbar AE, Wert SE, Askin F, Hamvas A, Whitsett JA (februar 2001). "A mutation in the surfactant protein C gene associated with familial interstitial lung disease". The New England Journal of Medicine. 344 (8): 573–9. doi:10.1056/NEJM200102223440805. PMID 11207353.
Glasser SW, Burhans MS, Korfhagen TR, Na CL, Sly PD, Ross GF, et al. (maj 2001). "Altered stability of pulmonary surfactant in SP-C-deficient mice". Proceedings of the National Academy of Sciences of the United States of America. 98 (11): 6366–71. Bibcode:2001PNAS...98.6366G. doi:10.1073/pnas.101500298. PMC 33474. PMID 11344267.